B 15i6 November 2014

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UK Standards for Microbiology Investigations
Investigation of Bile
Issued by the Standards Unit, Microbiology Services, PHE
Bacteriology | B 15 | Issue no: 6 | Issue date: 10.11.14 | Page: 1 of 19
© Crown copyright 2014
Investigation of Bile
Acknowledgments
UK Standards for Microbiology Investigations (SMIs) are developed under the
auspices of Public Health England (PHE) working in partnership with the National
Health Service (NHS), Public Health Wales and with the professional organisations
whose logos are displayed below and listed on the website https://www.gov.uk/ukstandards-for-microbiology-investigations-smi-quality-and-consistency-in-clinicallaboratories. SMIs are developed, reviewed and revised by various working groups
which are overseen by a steering committee (see
https://www.gov.uk/government/groups/standards-for-microbiology-investigationssteering-committee).
The contributions of many individuals in clinical, specialist and reference laboratories
who have provided information and comments during the development of this
document are acknowledged. We are grateful to the Medical Editors for editing the
medical content.
For further information please contact us at:
Standards Unit
Microbiology Services
Public Health England
61 Colindale Avenue
London NW9 5EQ
E-mail: standards@phe.gov.uk
Website: https://www.gov.uk/uk-standards-for-microbiology-investigations-smi-qualityand-consistency-in-clinical-laboratories
UK Standards for Microbiology Investigations are produced in association with:
Logos correct at time of publishing.
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UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Investigation of Bile
Contents
ACKNOWLEDGMENTS .......................................................................................................... 2
AMENDMENT TABLE ............................................................................................................. 4
UK SMI: SCOPE AND PURPOSE ........................................................................................... 5
SCOPE OF DOCUMENT ......................................................................................................... 7
SCOPE .................................................................................................................................... 7
INTRODUCTION ..................................................................................................................... 7
TECHNICAL INFORMATION/LIMITATIONS ........................................................................... 9
1
SAFETY CONSIDERATIONS .................................................................................... 10
2
SPECIMEN COLLECTION ......................................................................................... 10
3
SPECIMEN TRANSPORT AND STORAGE ............................................................... 11
4
SPECIMEN PROCESSING/PROCEDURE ................................................................. 11
5
REPORTING PROCEDURE ....................................................................................... 14
6
NOTIFICATION TO PHE OR EQUIVALENT IN THE DEVOLVED
ADMINISTRATIONS .................................................................................................. 14
APPENDIX: INVESTIGATION OF BILE ................................................................................ 16
REFERENCES ...................................................................................................................... 17
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Amendment Table
Each SMI method has an individual record of amendments. The current amendments
are listed on this page. The amendment history is available from
standards@phe.gov.uk.
New or revised documents should be controlled within the laboratory in accordance
with the local quality management system.
Amendment No/Date.
9/10.11.14
Issue no. discarded.
5.2
Insert Issue no.
6
Section(s) involved
Amendment
Whole document.
Hyperlinks updated to gov.uk.
Page 2.
Updated logos added.
Whole document.
Contents reviewed and restructured to improve the
flow of the document.
References.
Reviewed and updated.
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Investigation of Bile
UK SMI: Scope and Purpose
Users of SMIs
Primarily, SMIs are intended as a general resource for practising professionals
operating in the field of laboratory medicine and infection specialties in the UK. SMIs
also provide clinicians with information about the available test repertoire and the
standard of laboratory services they should expect for the investigation of infection in
their patients, as well as providing information that aids the electronic ordering of
appropriate tests. The documents also provide commissioners of healthcare services
with the appropriateness and standard of microbiology investigations they should be
seeking as part of the clinical and public health care package for their population.
Background to SMIs
SMIs comprise a collection of recommended algorithms and procedures covering all
stages of the investigative process in microbiology from the pre-analytical (clinical
syndrome) stage to the analytical (laboratory testing) and post analytical (result
interpretation and reporting) stages. Syndromic algorithms are supported by more
detailed documents containing advice on the investigation of specific diseases and
infections. Guidance notes cover the clinical background, differential diagnosis, and
appropriate investigation of particular clinical conditions. Quality guidance notes
describe laboratory processes which underpin quality, for example assay validation.
Standardisation of the diagnostic process through the application of SMIs helps to
assure the equivalence of investigation strategies in different laboratories across the
UK and is essential for public health surveillance, research and development activities.
Equal Partnership Working
SMIs are developed in equal partnership with PHE, NHS, Royal College of
Pathologists and professional societies. The list of participating societies may be
found at https://www.gov.uk/uk-standards-for-microbiology-investigations-smi-qualityand-consistency-in-clinical-laboratories. Inclusion of a logo in an SMI indicates
participation of the society in equal partnership and support for the objectives and
process of preparing SMIs. Nominees of professional societies are members of the
Steering Committee and Working Groups which develop SMIs. The views of nominees
cannot be rigorously representative of the members of their nominating organisations
nor the corporate views of their organisations. Nominees act as a conduit for two way
reporting and dialogue. Representative views are sought through the consultation
process. SMIs are developed, reviewed and updated through a wide consultation
process.
Quality Assurance
NICE has accredited the process used by the SMI Working Groups to produce SMIs.
The accreditation is applicable to all guidance produced since October 2009. The
process for the development of SMIs is certified to ISO 9001:2008. SMIs represent a
good standard of practice to which all clinical and public health microbiology

Microbiology is used as a generic term to include the two GMC-recognised specialties of Medical Microbiology (which includes
Bacteriology, Mycology and Parasitology) and Medical Virology.
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Investigation of Bile
laboratories in the UK are expected to work. SMIs are NICE accredited and represent
neither minimum standards of practice nor the highest level of complex laboratory
investigation possible. In using SMIs, laboratories should take account of local
requirements and undertake additional investigations where appropriate. SMIs help
laboratories to meet accreditation requirements by promoting high quality practices
which are auditable. SMIs also provide a reference point for method development. The
performance of SMIs depends on competent staff and appropriate quality reagents
and equipment. Laboratories should ensure that all commercial and in-house tests
have been validated and shown to be fit for purpose. Laboratories should participate
in external quality assessment schemes and undertake relevant internal quality control
procedures.
Patient and Public Involvement
The SMI Working Groups are committed to patient and public involvement in the
development of SMIs. By involving the public, health professionals, scientists and
voluntary organisations the resulting SMI will be robust and meet the needs of the
user. An opportunity is given to members of the public to contribute to consultations
through our open access website.
Information Governance and Equality
PHE is a Caldicott compliant organisation. It seeks to take every possible precaution
to prevent unauthorised disclosure of patient details and to ensure that patient-related
records are kept under secure conditions. The development of SMIs are subject to
PHE Equality objectives https://www.gov.uk/government/organisations/public-healthengland/about/equality-and-diversity.
The SMI Working Groups are committed to achieving the equality objectives by
effective consultation with members of the public, partners, stakeholders and
specialist interest groups.
Legal Statement
Whilst every care has been taken in the preparation of SMIs, PHE and any supporting
organisation, shall, to the greatest extent possible under any applicable law, exclude
liability for all losses, costs, claims, damages or expenses arising out of or connected
with the use of an SMI or any information contained therein. If alterations are made to
an SMI, it must be made clear where and by whom such changes have been made.
The evidence base and microbial taxonomy for the SMI is as complete as possible at
the time of issue. Any omissions and new material will be considered at the next
review. These standards can only be superseded by revisions of the standard,
legislative action, or by NICE accredited guidance.
SMIs are Crown copyright which should be acknowledged where appropriate.
Suggested Citation for this Document
Public Health England. (2014). Investigation of Bile. UK Standards for Microbiology
Investigations. B 15 Issue 6. https://www.gov.uk/uk-standards-for-microbiologyinvestigations-smi-quality-and-consistency-in-clinical-laboratories
Bacteriology | B 15 | Issue no: 6 | Issue date: 10.11.14 | Page: 6 of 19
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Investigation of Bile
Scope of Document
Type of Specimen
Bile
Scope
This SMI describes the processing and bacteriological investigation of bile.
This SMI should be used in conjunction with other SMIs.
Introduction
Biliary infection can produce significant morbidity and mortality and the prognosis
often depends upon whether biliary tract obstruction is present. Gram negative
bacteria (mainly Escherichia coli) are the cause of the majority of biliary infections
although Gram positive and anaerobic organisms are also found 1,2. Biliary infection
presents as either cholangitis or cholecystitis.
Bile is normally sterile, however colonisation may occur, frequently with a mixture of
aerobes and anaerobes originating from the gut3. Occasionally instrumentation or
stenting may lead to colonisation or infection, which may progress to bacteraemia4.
Fever, previous endoscopic or percutaneous biliary instrumentation, and bilioenteric
anastomosis are significant predictors of a positive bile culture2.
Cholangitis3
Cholangitis is the inflammation of the biliary ducts. It may present in two forms,
ascending or suppurative cholangitis. Both have similar pathology.
Ascending cholangitis5
Ascending cholangitis occurs when partial obstruction of the biliary ducts and bacterial
proliferation in the bile occur together3. Bacteria are shed intermittently into the
bloodstream. This can develop into suppurative cholangitis. Ascending cholangitis is a
common cause of sepsis following liver transplantation.
Suppurative cholangitis
Suppurative cholangitis occurs when an infected biliary system is completely
obstructed. Biliary pressure increases and bacteria are constantly shed into the
bloodstream. Diagnosis of infection can be made by aspirating bile and taking blood
cultures (B 37 - Investigation of Blood Cultures (for Organisms other than
Mycobacterium species).
Recurrent pyogenic cholangitis
Recurrent pyogenic cholangitis presents as episodes of right abdominal pain, biliary
obstruction and cholangitis and Gram negative septicaemia in patients that are
chronically infected with biliary parasites.
Cholecystitis
Cholecystitis is inflammation of the gall bladder. It is usually due to an infection that is
often secondary to the presence of gallstones. When the cystic duct is obstructed by a
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gallstone the hydrostatic pressure in the gallbladder lumen is increased. This
produces pain and infection frequently ensues.
Emphysematous Cholecystitis
Emphysematous cholecystitis is an acute infective cholecystitis involving gas-forming
organisms, most commonly Clostridium perfringens. Gangrene and perforation may
result.
Endoscopic Retrograde Cholangiopancreatography (ERCP)
One of a variety of imaging techniques used to study the biliary tree, whereby an
endoscope is passed from the gut via the ampulla of Vater into the biliary ducts. This
is minimally invasive but may cause biliary sepsis.
Organisms Isolated from Bile include3,5:

Enterobacteriaceae

Enterococcus species

Pseudomonads

Bacteroides species

Clostridium species

Anaerobes

Staphylococcus aureus

Salmonella
Other organisms may be isolated and should be given consideration depending on
clinical details.
Yeast Infections
Yeast infections are rare in normal individuals. They occur in older patients with
malignancy, immunocompromised patients, diabetic patients or in patients undergoing
antimicrobial treatment for other infections. Such infections may be confined to the
biliary tract or be a feature of more general candidosis. They usually involve Candida
albicans, but other Candida species have been reported2,6-8.
Parasitic Invasion
Parasitic invasion of the biliary tract occurs in patients from or in the developing world
or those who are immunosuppressed and may involve5:

Ascaris lumbricoides

Clonorchis sinensis

Opisthorchis species

Fasciola hepatica

Giardia lamblia

Cryptosporidium species

Microspora
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These are described in B 31 - Investigation of Specimens other than Blood for
Parasites.
Technical Information/Limitations
Limitations of UK SMIs
The recommendations made in UK SMIs are based on evidence (eg sensitivity and
specificity) where available, expert opinion and pragmatism, with consideration also
being given to available resources. Laboratories should take account of local
requirements and undertake additional investigations where appropriate. Prior to use,
laboratories should ensure that all commercial and in-house tests have been validated
and are fit for purpose.
Selective Media in Screening Procedures
Selective media which does not support the growth of all circulating strains of
organisms may be recommended based on the evidence available. A balance
therefore must be sought between available evidence, and available resources
required if more than one media plate is used.
Specimen Containers9,10
SMIs use the term “CE marked leak proof container” to describe containers bearing
the CE marking used for the collection and transport of clinical specimens. The
requirements for specimen containers are given in the EU in vitro Diagnostic Medical
Devices Directive (98/79/EC Annex 1 B 2.1) which states: “The design must allow
easy handling and, where necessary, reduce as far as possible contamination of, and
leakage from, the device during use and, in the case of specimen receptacles, the risk
of contamination of the specimen. The manufacturing processes must be appropriate
for these purposes”.
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1
Safety Considerations9-25
1.1
Specimen Collection, Transport and Storage9-14
Use aseptic technique.
Collect specimens in appropriate CE marked leak proof containers and transport in
sealed plastic bags.
Compliance with postal, transport and storage regulations is essential.
1.2
Specimen Processing9-25
Containment Level 2.
Laboratory procedures that give rise to infectious aerosols must be conducted in a
microbiological safety cabinet17.
Diagnostic work with clinical material that could possibly contain Hazard Group 3
organisms (Salmonella Typhi and Salmonella Paratyphi A,B & C,) does not normally
require full Containment Level 3 containment17 (paragraph 175).
If these Hazard Group 3 organisms are suspected, work should take place at a higher
containment level but full Containment Level 3 may not be required 17 (paragraphs
179-183).
If the work to be carried out requires the growth or manipulation of a Hazard Group 3
enteric biological agent then this has to be carried out under full Containment Level 3
conditions17 (paragraph 175).
Refer to current guidance on the safe handling of all organisms documented in this
SMI.
Note: S. Typhi and S. Paratyphi A, B and C cause severe and sometimes fatal
disease and laboratory acquired infections have been reported. S. Typhi vaccination is
available. Guidance is given in the Public Health England immunisation policy.
The above guidance should be supplemented with local COSHH and risk
assessments.
2
Specimen Collection
2.1
Type of Specimens
Bile
2.2
Optimal Time and Method of Collection26
For safety considerations refer to Section 1.1.
Collect specimens before antimicrobial therapy where possible26.
Unless otherwise stated, swabs for bacterial and fungal culture should be placed in
appropriate transport medium27-31.
Bile may be collected in theatre or from a closed drainage system by aspiration with a
needle and syringe.
Collect specimens other than swabs into appropriate CE marked leak proof containers
and place in sealed plastic bags.
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2.3
Adequate Quantity and Appropriate Number of Specimens26
Ideally, a minimum volume of 1mL.
Numbers and frequency of specimen collection are dependent on clinical condition of
patient.
3
Specimen Transport and Storage9,10
3.1
Optimal Transport and Storage Conditions
For safety considerations refer to Section 1.1.
Specimens should be transported and processed as soon as possible 26.
If processing is delayed, refrigeration is preferable to storage at ambient
temperature26.
The volume of specimen influences the transport time that is acceptable. Large
volumes of purulent material will maintain the viability of anaerobes for longer32-34.
Suggested transport times for varying volumes of specimen when examining for
anaerobes34:
Volume of aspirated material
Optimal time for transport to laboratory
<1mL
<10min
1mL
<30min
>2mL
<3hr
The recovery of anaerobes is compromised if the transport time exceeds 3hr.
4
Specimen Processing/Procedure9,10
4.1
Test Selection
Select a representative portion of specimen for appropriate procedures such as
examination for parasites (B 31 - Investigation of Specimens other than Blood for
Parasites) depending on clinical details.
4.2
Appearance
The presence of pus should be noted.
4.3
Sample Preparation
For safety considerations refer to Section 1.2.
4.4
Microscopy
4.4.1 Standard
Using a sterile pipette place one drop of specimen on to a clean microscope slide.
4.4.2 Supplementary
Microscopy for parasites – see B 31 - Investigation of Specimens other than Blood for
Parasites.
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If a Gram stain is required, spread one drop of the specimen with a sterile loop to
make a thin smear on a clean microscope slide.
4.5
Culture and Investigation
Using a sterile pipette inoculate each agar plate and enrichment broth, if included, with
specimen (see Q 5 - Inoculation of Culture Media for Bacteriology).
For the isolation of individual colonies, spread inoculum with a sterile loop.
4.5.1 Culture media, conditions and organisms
Clinical
details/
Specimen
Standard
media
Incubation
Bile
Target organism(s)
Temp
°C
Atmos
Time
Blood agar
35-37
5-10%
CO2
40-48hr
daily
CLED*/
MacConkey
agar
35-37
air
16-24hr
16hr
Any organism
Neomycin
fastidious
anaerobe agar
35-37
anaerobic
5 d**
5 d***
Anaerobes
Cultures
read
Target organism(s)
Salmonella species
conditions
Cholangitis
Cultures
read
Cholecystitis
For these situations, add the following:
Clinical
details/
Specimen
Supplementary
media
conditions
Salmonella
carriage/infecti
on
Bile
Mannitol
selenite F broth
then
subcultured to
XLD
Incubation
Temp
°C
Atmos
Time
35-37
air
16-24hr
N/A
35-37
air
16-24hr
16hr
* CLED agar has only been validated for urine specimens
** incubation may be extended to 14 days; in such cases plates should be read at 5 days and then left in the incubator/cabinet until
day 14
*** if the laboratory has an anaerobic cabinet plates may be read at 48 hours, otherwise they should be left until day 5
4.6
Identification
Refer to individual SMIs for organism identification.
4.6.1 Minimum level of identification in the laboratory
Note: All work on S. Typhi and S. Paratyphi A, B & C must be performed in a
microbiological safety cabinet in a Containment Level 3 room.
Anaerobes
"anaerobes" level
β-haemolytic streptococci
Lancefield group level
Coagulase negative staphylococci
"coagulase negative" level
Enterobacteriaceae (not Salmonella
species)
"coliforms" level
Enterococci
genus level
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P. aeruginosa
species level
Other Pseudomonads
"pseudomonads" level
Salmonella
S. Typhi, S. Paratyphi or other serogroup level
S. aureus
species level
Streptococci
genus or Lancefield group level
C. albicans
species level
Other Candida species
genus level
Parasites
see B 31 - Investigation of Specimens other than Blood for
Parasites
Organisms may be further identified if this is clinically or epidemiologically indicated.
4.7
Antimicrobial Susceptibility Testing
Refer to British Society for Antimicrobial Chemotherapy (BSAC) and/or EUCAST
guidelines.
4.8
Referral for Outbreak Investigations
N/A
4.9
Referral to Reference Laboratories
For information on the tests offered, turn around times, transport procedure and the
other requirements of the reference laboratory click here for user manuals and request
forms.
Organisms with unusual or unexpected resistance, and whenever there is a laboratory
or clinical problem, or anomaly that requires elucidation should be sent to the
appropriate reference laboratory.
Contact appropriate devolved national reference laboratory for information on the tests
available, turn around times, transport procedure and any other requirements for
sample submission:
England and Wales
https://www.gov.uk/specialist-and-reference-microbiology-laboratory-tests-andservices
Scotland
http://www.hps.scot.nhs.uk/reflab/index.aspx
Northern Ireland
http://www.publichealth.hscni.net/directorate-public-health/health-protection
β-haemolytic
streptococci
Serotying
S. aureus
Spa Typing
Salmonella
Serotyping and phage typing (if applicable)
Fungi
Identification and/or susceptibility testing
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5
Reporting Procedure
5.1
Microscopy
Report on WBCs and organisms detected.
Microscopy for parasites – see B 31 - Investigation of Specimens other than Blood for
Parasites.
5.1.1 Microscopy reporting time
Urgent microscopy results to be telephoned or sent electronically.
Written report 16–72hr.
5.2
Culture
Report clinically significant organisms isolated (with an appropriate comment on
possible contamination or overgrowth if the specimen is from a collection bag or Ttube) or
Report: other growth or absence of growth.
Also, report results of supplementary investigations.
Culture reporting time.
Clinically urgent results to be telephoned or sent electronically.
Written report, 16 – 72hr stating, if appropriate, that a further report will be issued.
Supplementary investigations Parasites – see B 31 - Investigation of Specimens other
than Blood for Parasites.
5.3
Antimicrobial Susceptibility Testing
Report susceptibilities as clinically indicated. Prudent use of antimicrobials according
to local and national protocols is recommended.
6 Notification to PHE35,36 or Equivalent in the
Devolved Administrations37-40
The Health Protection (Notification) regulations 2010 require diagnostic laboratories to
notify Public Health England (PHE) when they identify the causative agents that are
listed in Schedule 2 of the Regulations. Notifications must be provided in writing, on
paper or electronically, within seven days. Urgent cases should be notified orally and
as soon as possible, recommended within 24 hours. These should be followed up by
written notification within seven days.
For the purposes of the Notification Regulations, the recipient of laboratory
notifications is the local PHE Health Protection Team. If a case has already been
notified by a registered medical practitioner, the diagnostic laboratory is still required
to notify the case if they identify any evidence of an infection caused by a notifiable
causative agent.
Notification under the Health Protection (Notification) Regulations 2010 does not
replace voluntary reporting to PHE. The vast majority of NHS laboratories voluntarily
report a wide range of laboratory diagnoses of causative agents to PHE and many
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Investigation of Bile
PHE Health protection Teams have agreements with local laboratories for urgent
reporting of some infections. This should continue.
Note: The Health Protection Legislation Guidance (2010) includes reporting of Human
Immunodeficiency Virus (HIV) & Sexually Transmitted Infections (STIs), Healthcare
Associated Infections (HCAIs) and Creutzfeldt–Jakob disease (CJD) under
‘Notification Duties of Registered Medical Practitioners’: it is not noted under
‘Notification Duties of Diagnostic Laboratories’.
https://www.gov.uk/government/organisations/public-health-england/about/ourgovernance#health-protection-regulations-2010
Other arrangements exist in Scotland37,38, Wales39 and Northern Ireland40.
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Investigation of Bile
Appendix: Investigation of Bile
Prepare specimens
For all samples
Additional media
Cholangitis
Cholecystitis
Salmonella carriage
infection
CLED / MacConkey
agar
Blood agar
Incubate at 35-37°C
In 5-10% CO2
40 - 48hr
Read daily
Incubate at 35-37°C
In air
16 -24hr
Read at 16hr
Neomycin / Fastidious
anaerobe agar
Incubate at 35-37°C
Anaerobically
48hr
Read at 48hr
Mannitol selenite
F broth
Incubate at 35-37°C
In air
16 -24hr
Subculture to XLD
media
Incubate at 35-37°C
In air
16 -24hr
Read at 16hr
Any organism
Refer to IDs
Anaerobes
ID 8, 14, 25
Salmonella sp refer to
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ID 24
Investigation of Bile
References
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2. Brody LA, Brown KT, Getrajdman GI, Kannegieter LS, Brown AE, Fong Y, et al. Clinical factors
associated with positive bile cultures during primary percutaneous biliary drainage. J Vasc Interv
Radiol 1998;9:572-8.
3. Sinanan MN. Acute cholangitis. Infect Dis Clin North Am 1992;6:571-99.
4. Hochwald SN, Burke EC, Jarnagin WR, Fong Y, Blumgart LH. Association of preoperative biliary
stenting with increased postoperative infectious complications in proximal cholangiocarcinoma.
Arch Surg 1999;134:261-6.
5. Kinney TP. Management of ascending cholangitis. Gastrointest Endosc Clin N Am 2007;17:289306, vi.
6. Ehrenstein BP, Salamon L, Linde HJ, Messmann H, Scholmerich J, Gluck T. Clinical determinants
for the recovery of fungal and mezlocillin-resistant pathogens from bile specimens. Clinical
Infectious Diseases 2002;34:902-8.
7. Irani M, Truong LD. Candidiasis of the extrahepatic biliary tract. Arch Pathol Lab Med
1986;110:1087-90.
8. Cervia JS, Murray HW. Fungal cholecystitis and AIDS. J Infect Dis 1990;161:358.
9. European Parliament. UK Standards for Microbiology Investigations (SMIs) use the term "CE
marked leak proof container" to describe containers bearing the CE marking used for the collection
and transport of clinical specimens. The requirements for specimen containers are given in the EU
in vitro Diagnostic Medical Devices Directive (98/79/EC Annex 1 B 2.1) which states: "The design
must allow easy handling and, where necessary, reduce as far as possible contamination of, and
leakage from, the device during use and, in the case of specimen receptacles, the risk of
contamination of the specimen. The manufacturing processes must be appropriate for these
purposes".
10. Official Journal of the European Communities. Directive 98/79/EC of the European Parliament and
of the Council of 27 October 1998 on in vitro diagnostic medical devices. 7-12-1998. p. 1-37.
11. Health and Safety Executive. Safe use of pneumatic air tube transport systems for pathology
specimens. 9/99.
12. Department for transport. Transport of Infectious Substances, 2011 Revision 5. 2011.
13. World Health Organization. Guidance on regulations for the Transport of Infectious Substances
2013-2014. 2012.
14. Home Office. Anti-terrorism, Crime and Security Act. 2001 (as amended).
15. Advisory Committee on Dangerous Pathogens. The Approved List of Biological Agents. Health and
Safety Executive. 2013. p. 1-32
16. Advisory Committee on Dangerous Pathogens. Infections at work: Controlling the risks. Her
Majesty's Stationery Office. 2003.
17. Advisory Committee on Dangerous Pathogens. Biological agents: Managing the risks in
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